Thiol-Disulfide Exchange Coordinates the Release of Nitric Oxide and Dexamethasone for Synergistic Regulation of Intestinal Microenvironment in Colitis  

作　　者：Junna Lu Tongfei Shi Chengxin Shi Fangman Chen Chao Yang Xiaochun Xie Zheng Wang He Shen Jiaqi Xu Kam W.Leong Dan Shao 

机构地区：[1]School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou,Guangdong 510006,China [2]National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangdong 510006,China [3]Department of Plastic and Aesthetic Center,The First Affliated Hospital of Zhejiang University,Hangzhou 310000,China [4]Department of Biomedical Engineering,Columbia University,New York,NY 10027,USA [5]School of Medicine,South China University of Technology,Guangzhou,Guangdong 510006,China [6]CAS Key Laboratory of Nano-Bio Interface,Suzhou Institute of Nano-Tech and NanoBionics,Chinese Academy of Sciences,Suzhou 215123,China [7]CAS Key Laboratory for Biomedical Efects of Nanomaterials&Nanosafety,CAS Center for Excellence in Nanoscience,National Center for Nanoscience and Technology,Beijing 100190,China [8]Guangdong Provincial Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China [9]Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,South China University of Technology,Guangzhou 510006,China

出　　处：《Research》2024年第2期285-300,共16页研究（英文）

基　　金：supported by the National Natural Science Foundation of China(grant nos.82072049 and 32271388);the Fundamental Research Funds for the Central Universities.

摘　　要：The cell-specific functions of nitric oxide(NO)in the intestinal microenvironment orchestrate its therapeutic effects in ulcerative colitis.While most biomaterials show promise by eliciting the characteristics of NO,the insufficient storage,burst release,and pro-inflammatory side effects of NO remain as challenges.Herein,we report the development of thiol-disulfide hybrid mesoporous organosilica nanoparticles(MONs)that improve the storage and sustained release of NO,broadening the therapeutic window of NO-based therapy against colitis.The tailored NO-storing nanomaterials coordinated the release of NO and the immunoregulator dexamethasone(Dex)in the intestinal microenvironment,specifically integrating the alleviation of oxidative stress in enterocytes and the reversal of NO-exacerbated macrophage activation.Mechanistically,such a synchronous operation was achieved by a self-motivated process wherein the thiyl radicals produced by NO release cleaved the disulfide bonds to degrade the matrix and release Dex via thiol-disulfide exchange.Specifically,the MON-mediated combination of NO and Dex greatly ameliorated intractable colitis compared with 5-aminosalicylic acid,even after delayed treatment.Together,our results reveal a key contribution of synergistic modulation of the intestinal microenvironment in NO-based colitis therapy and introduce thiol-disulfide hybrid nanotherapeutics for the management of inflammatory diseases and cancer.

关 键 词：sustained RELEASE DISULFIDE 

分 类 号：R574[医药卫生—消化系统]